The objective of the study is to complete our investigations concerning the intracerebral pathways involved in the development of vasospasm after an experimental subarachnoid haemorrhage (SAH) in the rat, and to examine if the findings obtained in the rat also are valid for primates. The data to be verified are that the A2 and/or A1 nuclei in the medulla oblongata via their projections in the central tegmental tract to the median eminence region, are necessary for the development of spasm also in the monkey post SAH, and that the vasoactive substance similar to that liberated into the cerebrospinal fluid in SAH patients and rats also is liberated in monkeys with a SAH. Further, we plan to verify if afferents from the brain vessels terminating in the A2 nucleus in the rat, do the same in the monkey. The aim of the study is the design of a selective therapy against vasospasm. The knowledge of the basic mechanism behind spasm gives a rationale for the design. Blockage of the liberation of, or production of an antigen against the vasoactive substance are possible methods of treatment. Blockage of the afferent input to A2 could be another solution. A SAH model will be developed in the squirrel monkey. The effect of the blood will be evaluated by four vessel angiography with delineation of the time course of vasospasm, or by autoradiographic CBF- and CMRglu measurements, preferably in the late phase of vasospasm. Selective stereotactic chemical or electrothermic lesions with adequate microscopical, biochemical and endocrinological control will be developed in the monkey. Subsequent to the lesions, the monkeys will be subjected to a SAH and the effect of the cisternal blood will be evaluated by angiography, CBF- and CMRglu measurements. Parallel to the monkey experiments, we plan to continue the purification and hopefully finish the sequence analysis of the vasoactive substance in SAH cerebrospinal fluid and thereafter start therapeutic trials.